Primary amines, reactions with acetylenic

Vinyl- and acetylenic tricarbonyl compounds are reactive dienophilic components in Diels-Alder reactions. Cycloadditions of these compounds with substituted butadienes were recently used to develop a new synthetic approach to indole derivatives [14] (Scheme 2.9) by a three-step procedure including (i) condensation with primary amines, (ii) dehydration and (iii) DDQ oxidation. 

Similar reactions with primary and secondary amines result in the formation of 3-aUcylamino- or 3-dialkylamino-l-butyne in 30-80% yield (TON = 3-9) [243-247]. In one example, the TOP could be estimated as 0.2 h" [246]. Enamines were proposed as reaction intermediates. It was later shown that enamines effectively react with terminal aUcynes, including acetylene, to afford the expected aminoalkynes without catalyst or, more rapidly, sometimes exothermically, in the presence of CujCf [248]. Aromatic amines do not react under the same conditions. However, in the presence of organic acids, e.g. acetic acid, 3-arylamino-l-butynes can be isolated in moderate yields (Eq. 4.59) [246, 247, 249]. 

High yields of -substituted allenic primary amines 227 are obtained by the CuBr-Me2S-or NiCh Ph2PCH2CH2CH2PPh2-catalysed reaction of the acetylene derivative 226 with aryl Grignard compounds and subsequent deprotection by flash chromatography219. 

The reaction of amines with acetylenic esters has been investigated in detail by several groups of workers. In general, primary amines react... 

In sharp contrast, amination of diphenylacetylene with primary amines induced by dimethyltitanocene596 or the reaction of terminal acetylenes with various primary amines in the presence of [Ru3(CO)i2]597 results in the formation of the corresponding imines ... 

A coupling procedure particularly suited to the synthesis of unsymmetrical diacetylenes involves the reaction of a terminal acetylene with a 1-bromo-acetylene in the presence of a catalyst consisting of a solution of copper(i) chloride in a primary amine to which small quantities of hydroxylamine hydrochloride is added (the Cadiot-Chodkiewicz coupling). 

Cadmium acetate-Zinc acetate. The catalyst, prepared by heating a mixture of 2.5 g. each of cadmium acetate dihydrate and zinc acetate dihydrate to remove the water of hydration, promotes addition of primary aliphatic amines to acetylene to give ethylidenimines. Thus ethylamine, heated with acetylene and catalyst in an autoclave at 120-140° for 29 hrs., afforded N-ethylethylidenimine (1). Catalyzed reaction... 

We further explored the steric effect of this Michael addition-cyclization reaction sequence. A series of secondary amines 13a-f were prepared and subjected to the Michael addition and acid-induced cyclization (Scheme 6) [12]. The results are summarized in Table 2. In general, we found that the secondary amines were less reactive in this Michael addition-cyclization reaction sequence. The p-toluene acetylenic sulfoxide la was not reactive enough and only the stronger electron-withdrawing o-nitrophenyl acetylenic sulfoxide 1 b achieved the transformation. In contrast to the primary amine approach, the secondary amine approach resulted in a reversed diastereoselectivity bias with compounds 14 as the major isolated products (except 13e). In general, a lower reaction temperature and increase in the steric hindrance of the secondary amine improved the diastereoselectivity. Exceptionally good diastereoselectivity was observed for the cyclization of 13 f (Scheme 6) (Table 2)... 

Treatment of 75 with lithium acetylide ethylenediamine complex afforded the acetylene derivative 78 (85%), which was transformed into the vinyl alcohol 79 by partial hydrogenation using Lindlar catalyst. Employing the Mitsunobu reaction, compound 79 was transformed into the phthalimide 80, which was converted into the benzamide 82 (64%) via the primary amine 81 by sequential deacylation and benzoylation. When the... 

Several D-ribofuranosyl [113] and L-arabinofuranosyl 1,2,3-triazole derivatives [114] such as 119 have been prepared by cycloaddition of the corresponding glycosyl azide to 2-ethoxycarbonyl-2-oxoethylidene-triphenylphos-phorane, followed by reaction with methanolic ammonia or primary or secondary amines (Scheme 29). Some of prepared nucleosides proved to be potent inhibitors of HIV-1 replication. Phosphorus ylides containing an a-oxo group in the chain behave in a similar way as activated acetylenes with electron-donating groups [108[. Presimiably the azide adds to the enolate form of the ylide, followed by elimination of PhsPO [108]. 

An aqueous, green, simple, and direct synthetic procedure was reported by our group in 2009 for the synthesis of rhodanine derivatives via the three-component method, which began with the reaction of carbon disulfide, primary amines, and acetylenic esters under neutral conditions [44] to give rhodanine 50. This procedure was completely a green and eco-friendly method (Scheme 9.22). 

Scheme 4-15. Reaction of dodecacarbonyltriiron with primary amines and acetylenes to form cyclic imides.

Primary dialkylboranes react readily with most alkenes at ambient temperatures and dihydroborate terminal acetylenes. However, these unhindered dialkylboranes exist in equiUbtium with mono- and ttialkylboranes and cannot be prepared in a state of high purity by the reaction of two equivalents of an alkene with borane (35—38). Nevertheless, such mixtures can be used for hydroboration if the products are acceptable for further transformations or can be separated (90). When pure primary dialkylboranes are required they are best prepared by the reduction of dialkylhalogenoboranes with metal hydrides (91—93). To avoid redistribution they must be used immediately or be stabilized as amine complexes or converted into dialkylborohydtides. 

Nickel peroxide is a solid, insoluble oxidant prepared by reaction of nickel (II) salts with hypochlorite or ozone in aqueous alkaline solution. This reagent when used in nonpolar medium is similar to, but more reactive than, activated manganese dioxide in selectively oxidizing allylic or acetylenic alcohols. It also reacts rapidly with amines, phenols, hydrazones and sulfides so that selective oxidation of allylic alcohols in the presence of these functionalities may not be possible. In basic media the oxidizing power of nickel peroxide is increased and saturated primary alcohols can be oxidized directly to carboxylic acids. In the presence of ammonia at —20°, primary allylic alcohols give amides while at elevated temperatures nitriles are formed. At elevated temperatures efficient cleavage of a-glycols, a-ketols... 

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